A major program in the mass spectrometry laboratory at NIEHS is the application of tandem mass spectrometric techniques (MS/MS) to the structure elucidation of compounds of interest in the environmental health sciences. The structure determination of these compounds is basic to understanding the interactions of compounds within the body, especially those due to altered metabolism and those arising through the interactions of xenobiotics and biomolecules. These techniques are important because samples of interest are often complex mixtures and because the ionization techniques applicable to these samples often provide little or no structura information. Our approach to the development of MS/MS techniques is twofold: structure elucidation and increasing the sensitivity of the technique. Current projects in the area of structure determination include: 1) development of hybrid MS/MS techniques in combination with electrospray ionization; 2) determination of the structure of macrolide antibiotics and the bacterial enzymatic deactivation products; 3) structure determination of peptides expressed by flu-infected cells that are recognized by T-cells as indicative of infected cells (biological model systems for AIDS infected cell recognition); 4) application of MS/MS to the structure determination of spin-trapped free radicals in conbination with electrospray ionization; 5) development of selected reaction monitoring in combination with in vivo microdialysis for the determination of pharmacokinetics of compounds of toxicological interest; 6) development of ultrasensitive MS/MS techniques in combination with CE and packed nanoscale columns on a mass spectrometer with array detection (in collaboration with the University of Nebraska).